This application focuses on the mechanism by which A-kinase anchoring proteins (AKAPs), and more specifically AKAP79, promotes the cellular compartmentalization of protein kinases and phosphatases down-stream of receptors that activate them and upstream of target proteins. Aim 1 will elucidate the functional consequences of AKAP79-mediated targeting of PKA to the beta2-adrenergic receptor and map sites of interaction on both the receptor and the anchoring protein. In Aim 2, a combination of biochemical and electrophysiological approaches will be used to examine whether AKAP79-mediated anchoring of PKA and PP-2B close to the AMPA channel augments or attenuates channel activity by promoting its phosphorylation or dephosphorylation, respectively. In Aim 3, experiments are proposed to determine if the interaction of AKAP79 with PSD95, an integral component of the postsynaptic density, links upstream signaling complexes with downstream elements such as NMDA or AMPA glutamate receptors.